Is VPS13B p.Ser170= (c.510C>T) pathogenic?

VPS13B p.Ser170= (c.510C>T) is classified Likely benign in VPS13B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-26). Ultra-rare (popmax 0.022%, sas); Associated with Cohen syndrome.

What condition is associated with VPS13B p.Ser170= (c.510C>T)?

VPS13B p.Ser170= (c.510C>T) is associated with Cohen syndrome (ClinVar).

How common is VPS13B p.Ser170= (c.510C>T) in the general population?

VPS13B p.Ser170= (c.510C>T) is ultra-rare (popmax 0.022%, sas) (gnomAD).

VPS13B p.Ser170=

c.510C>T · rs749836132 · VCV724979

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.022%, sas)

Conditions

Cohen syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP -4.1, phastCons 1
Overall
CADD	13.86	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.022% South Asian · 20/91,058 alleles

Filtering AF 0.0145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.00211% 34/1,613,434 alleles · ultra-rare exomes 28/1,461,438 · genomes 6/151,996 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.022%	4,553
African / African-American	0.00935%	10,694
Remaining individualsnot grpmax-eligible	0.0016%	62,466
European (non-Finnish)	0.000509%	196,614

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: VPS13B
Protein: p.Ser170=
Coding: c.510C>T
MANE Select: NM_152564
dbSNP: rs749836132
Type: single nucleotide variant
Location: chr8:99103050 (GRCh38)
Gene constraint: LOEUF 0.708 · pLI <0.01 (gnomAD)
Residue 170: a UniProt-annotated variant site (in coh1); a UniProt-annotated variant site (in coh1; leads to an accumulation of liquid droplets and accelerates differentiation of adipose cells; response to insulin is abnormal)

Full VPS13B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cohen syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

VPS13B c.10867+1G>A Likely pathogenic ★★ same condition
VPS13B c.10868-2A>G Likely pathogenic ★★ same condition
VPS13B c.11044+1G>A Pathogenic/Likely pathogenic ★★ same condition
VPS13B c.11392+1G>T Likely pathogenic ★★ same condition
VPS13B c.11496-2A>G Pathogenic ★★ same condition
VPS13B c.11746-1G>A Pathogenic/Likely pathogenic ★★ same condition
VPS13B c.1843+1G>A Likely pathogenic ★★ same condition
VPS13B c.2516-2A>G Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/vps13b-p-ser170 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown